Epicardial cells' action potential durations (APD) are shorter than those of the underlying endocardium. Two theories have been advanced to explain this APD difference. One theory is that there are regional differences in the Na-K membrane pump, the other is that endocardial Purkinje fibers electronically influence endocardial muscle cells' APD's and make them longer. I propose to test these theories in several ways: 1) I will see if there are differences in the responses of endocardial and epicardial APD's to poisoning of the Na-K pump with ouabain. APD's will be measured with microelectrodes in LV tissue. 2) I will measure directly the endocardial and epicardial ouabain-sensitive Na-K ATPase activity. 3) I will determine, in vivo, with multielectrode needles the relationship between effective refractory period and distance across the LV wall to see if it is consistent with electrotonus. 4) I will use microelectrodes or unipolar electrodes to determine, in vitro, the transmural APD distribution in LV slices, then excise the Purkinje fiber layer and see how the APD distribution changes. 5) Finally, I will evaluate with a computer model, linking simulated Purkinje cells to ventricular muscle cells, the feasibility of the proposed interaction between the Purkinje fibers and ventricular muscle cells. The results of these studies will provide significant insights into the mechanism(s) causing epicardial cell APD's to be shorter then endocardial ones.